Inhibition of junctional protein disruption by 2,4,6-trihydroxy-3-geranyl acetophenone in lipopolysaccharide-induced endothelial hyperpermeability via GEF-H1/RhoA/ROCK pathway
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View abstract on PubMed
Summary
This summary is machine-generated.2,4,6-Trihydroxy-3-geranyl acetophenone (tHGA) protects endothelial barrier integrity by preserving junctional proteins ZO-1, occludin, and VE-cadherin. This compound may treat permeability-related disorders.
Area Of Science
- Pharmacology
- Cell Biology
- Biochemistry
Background
- Endothelial hyperpermeability contributes to various disorders.
- 2,4,6-Trihydroxy-3-geranyl acetophenone (tHGA) from Melicope pteleifolia shows barrier protective effects.
- tHGA inhibits endothelial hyperpermeability by affecting the F-actin cytoskeleton.
Purpose Of The Study
- Investigate tHGA's effects on junctional proteins (ZO-1, occludin, VE-cadherin).
- Dissect signalling pathways involved in tHGA's protective mechanism against LPS-induced disruption.
- Identify the molecular target of tHGA.
Main Methods
- Human Umbilical Vein Endothelial Cells (HUVECs) were pretreated with tHGA before LPS induction.
- Assessed endothelial barrier function using Transendothelial Electrical Resistance (TEER).
- Examined junctional protein integrity, localization, and expression via immunofluorescence and Western Blotting; gene expression via RT-qPCR; and signalling pathways (MLC, NF-κB p65, MAPKs) via Western Blotting. Molecular docking was used to predict ROCK1 interaction.
Main Results
- tHGA significantly preserved junctional integrity, inhibiting delocalization and downregulation of ZO-1, occludin, and VE-cadherin.
- tHGA inactivated MLC, NF-κB p65, p38 MAPK, and ERK MAPK, primarily via the GEF-H1/RhoA/ROCK pathway.
- Molecular docking predicted ROCK1 as a direct molecular target of tHGA.
Conclusions
- tHGA effectively maintains endothelial barrier function by protecting junctional proteins and modulating key inflammatory signalling pathways.
- tHGA demonstrates potential as a therapeutic agent for preventing or treating permeability-related disorders.
- ROCK1 is identified as a potential molecular target for tHGA's therapeutic action.
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